Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies

Bertha A Brodin1, Krister Wennerberg2,3, Elisabet Lidbrink4

  • 1Department of Microbiology Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. bertha.brodin@ki.se.

British Journal of Cancer
|February 13, 2019
PubMed
Abstract

Insights

Patient-derived sarcoma cells offer a practical model for drug discovery. This study identified Dasatinib as a potential targeted therapy for sarcomas with specific chromosomal translocations.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Sarcoma diagnosis and treatment are challenging due to heterogeneity and low incidence.
  • Current chemotherapy offers limited clinical responses, primarily for advanced disease.
  • Targeted therapies are scarce despite identified genomic aberrations in some sarcoma subtypes.

Observation:

  • Patient-derived sarcoma cells were cultured and characterized from 14 sarcomas and 5 healthy mesenchymal primary cell cultures.
  • Cells underwent gene panel sequencing, cancer driver gene expression analysis, and detection of fusion oncoproteins.
  • Sensitivity to 525 anti-cancer agents, both approved and investigational, was evaluated.

Findings:

  • A 58% success rate was achieved in establishing soft tissue sarcoma cultures from patient biopsies.
  • Genomic profiling and drug sensitivity testing identified targeted inhibitors, including the cSrc inhibitor Dasatinib, effective against sarcomas with chromosomal translocations.
  • Ex vivo drug sensitivity of patient sarcoma cells correlated with in vivo patient treatment responses.

Implications:

  • Patient-derived sarcoma cells in vitro serve as valuable models for genotypic and phenotypic drug screening.
  • This approach can identify effective drugs for sarcoma patients with limited treatment options.
  • The findings support personalized medicine strategies in sarcoma treatment by matching drugs to specific sarcoma profiles.

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